PDBsum entry 3d8f

Protein binding

PDB id: 3d8f

Contents

Protein chains

127 a.a. *

126 a.a. *

Ligands

PO4 ×2

Waters ×22

* Residue conservation analysis

PDB id:

3d8f

Name:

Protein binding

Title:

Crystal structure of the human fe65-ptb1 domain with bound phosphate (trigonal crystal form)

Structure:

Amyloid beta a4 precursor protein-binding family b member 1. Chain: a, b, c, d. Fragment: phosphotyrosine binding domain 1. Synonym: fe65-ptb1, fe65 protein. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: apbb1, fe65, rir. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.70Å R-factor: 0.245 R-free: 0.313

Authors:

J.Radzimanowski,S.Ravaud,I.Sinning,K.Wild

Key ref:

J.Radzimanowski et al. (2008). Crystal structure of the human Fe65-PTB1 domain. J Biol Chem, 283, 23113-23120. PubMed id: 18550529 DOI: 10.1074/jbc.M800861200

Date:

23-May-08 Release date: 10-Jun-08

Protein chains

O00213  (APBB1_HUMAN) -  Amyloid beta precursor protein binding family B member 1 from Homo sapiens

Seq: 710 a.a.

Struc: 127 a.a.*

Protein chains

O00213  (APBB1_HUMAN) -  Amyloid beta precursor protein binding family B member 1 from Homo sapiens

Seq: 710 a.a.

Struc: 126 a.a.*

* PDB and UniProt seqs differ at 5 residue positions (black crosses)

Enzyme reactions

• Enzyme class: Chains A, B, C, D: E.C.?

DOI no: 10.1074/jbc.M800861200

J Biol Chem 283:23113-23120 (2008)

PubMed id: 18550529

Crystal structure of the human Fe65-PTB1 domain.

J.Radzimanowski, S.Ravaud, S.Schlesinger, J.Koch, K.Beyreuther, I.Sinning, K.Wild.

ABSTRACT

The neuronal adaptor protein Fe65 is involved in brain development, Alzheimer disease amyloid precursor protein (APP) signaling, and proteolytic processing of APP. It contains three protein-protein interaction domains, one WW domain, and a unique tandem array of phosphotyrosine-binding (PTB) domains. The N-terminal PTB domain (Fe65-PTB1) was shown to interact with a variety of proteins, including the low density lipoprotein receptor-related protein (LRP-1), the ApoEr2 receptor, and the histone acetyltransferase Tip60. We have determined the crystal structures of human Fe65-PTB1 in its apo- and in a phosphate-bound form at 2.2 and 2.7A resolution, respectively. The overall fold shows a PTB-typical pleckstrin homology domain superfold. Although Fe65-PTB1 has been classified on an evolutionary basis as a Dab-like PTB domain, it contains attributes of other PTB domain subfamilies. The phosphotyrosine-binding pocket resembles IRS-like PTB domains, and the bound phosphate occupies the binding site of the phosphotyrosine (Tyr(P)) within the canonical NPXpY recognition motif. In addition Fe65-PTB1 contains a loop insertion between helix alpha2 and strand beta2(alpha2/beta2 loop) similar to members of the Shc-like PTB domain subfamily. The structural comparison with the Dab1-PTB domain reveals a putative phospholipid-binding site opposite the peptide binding pocket. We suggest Fe65-PTB1 to interact with its target proteins involved in translocation and signaling of APP in a phosphorylation-dependent manner.

Selected figure(s)

Figure 3.
Phosphate binding to Fe65-PTB1 suggests phosphotyrosine-dependent peptide interactions. A, close-up view of the Fe65-PTB1 Tyr(P) binding pocket. The hydrogen-bonding network of the phosphate group is indicated by dashed lines. B, superposition of phosphate-bound Fe65-PTB1 with the IRS-1 PTB domain (PDB code 1irs). The bound NPApY motif of the bound peptide to IRS-1 is shown together with the two respective IRS-1 arginine residues of the binding pocket (gray). C, phosphate-bound Fe65-PTB1 superposed to the Dab1/APP nonphosphorylated peptide, including the NPTY motif (PDB code 1oqn).

Figure 4.
The putative phospholipid-binding site. A, Fe65-PTB1 (color ramps as in Figs. 2 and 3) superposed with the Dab1-PTB-APP-IP[3] complex (PDB code 1oqn) shown in gray and black. Residues involved in IP[3] binding and the equivalent three arginines of Fe65-PTB1 are given. Although helix α2 in Dab1 is elongated by two turns, Fe65-PTB1 contains a long and flexible α2/β2 loop. B, electrostatic surface potential of the Dab1-PTB domain showing the highly positively charged phospholipid binding crown responsible for IP[3] binding (stick model). Color scheme is as in Fig. 2. C, Fe65-PTB1 oriented in the same way with superposed IP[3] taken from the Dab1-PTB structure.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2008, 283, 23113-23120) copyright 2008.

Figures were selected by the author.